Off-label application of intravenous immunoglobulin (IVIG) for treatment of Cogan's syndrome during pregnancy.

We report the case of a woman with Cogan's syndrome concomitant with the wish to have children. After three major flares of the disease that led to unilateral deafness, immunosuppressive therapy with prednisolone and azathioprine was started. Because of the severe side effects, an off-label therapy with intravenous immunoglobulin (IVIG) was initiated, under which our patient has since given birth to three healthy children.

BCL11B mutations in patients affected by a neurodevelopmental disorder with reduced type 2 innate lymphoid cells.

The transcription factor BCL11B is essential for development of the nervous and the immune system, and Bcl11b deficiency results in structural brain defects, reduced learning capacity, and impaired immune cell development in mice. However, the precise role of BCL11B in humans is largely unexplored, except for a single patient with a BCL11B missense mutation, affected by multisystem anomalies and profound immune deficiency. Using massively parallel sequencing we identified 13 patients bearing heterozygous germline alterations in BCL11B.

Neutrophil Extracellular Traps Contain Selected Antigens of Anti-Neutrophil Cytoplasmic Antibodies.

Neutrophil extracellular traps (NETs) are chromatin filaments decorated with enzymes from neutrophil cytoplasmic granules. Anti-neutrophil cytoplasmic antibodies (ANCAs) bind to enzymes from neutrophil cytoplasmic granules and are biomarkers for the diagnosis of systemic vasculitides. ANCA diagnostics are based on indirect immunofluorescence (IIF) of ethanol-fixed neutrophils.

Plasma contact system activation drives anaphylaxis in severe mast cell-mediated allergic reactions.

Background: Anaphylaxis is an acute, potentially lethal, multisystem syndrome resulting from the sudden release of mast cell-derived mediators into the circulation.

Objectives And Methods: We report here that a plasma protease cascade, the factor XII-driven contact system, critically contributes to the pathogenesis of anaphylaxis in both murine models and human subjects.

Results: Deficiency in or pharmacologic inhibition of factor XII, plasma kallikrein, high-molecular-weight kininogen, or the bradykinin B2 receptor, but not the B1 receptor, largely attenuated allergen/IgE-mediated mast cell hyperresponsiveness in mice.

Peripheral blood biomarkers for the characterization of alloimmune reactivity after pediatric liver transplantation.

Individualization of immunosuppressive medications is an important objective in transplantation medicine. Reliable biomarkers to distinguish between patients dependent from intensive immunosuppressive therapy and those where therapy can be minimized among pediatric transplant recipients receiving immunosuppressive medications are still not established. We evaluated the potential of cross-sectional quantification of regulatory T cells, lymphocyte subsets, and cytokine concentrations as biomarkers in 60 pediatric liver transplant recipients with AR, CR, or normal graft function and in 11 non-transplanted patients.

Dynamic development of glucocorticoid resistance during autoimmune neuroinflammation.

Context: Glucocorticoids (GC) are powerful endogenous and therapeutic modulators of inflammation and play a critical role for controlling autoimmunity. GC resistance can be seen in patients with cell-mediated autoimmune disorders, but it is unknown whether this represents a stable trait or a state.

Objective: The objective of the study was to determine whether GC resistance of T cell responses is dynamically regulated in experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS).

Decreased hydrocortisone sensitivity of T cell function in multiple sclerosis-associated major depression.

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the CNS with a high prevalence of depression. Both MS and depression have been linked to elevated cortisol levels and inflammation, indicating disturbed endocrine-immune regulation. An imbalance in mineralocorticoid versus glucocorticoid signaling in the CNS has been proposed as a pathogenetic mechanism of depression.

Endocrine and immune substrates of depressive symptoms and fatigue in multiple sclerosis patients with comorbid major depression.

Objective: Depression and fatigue are among the most common symptoms of multiple sclerosis (MS). These symptoms frequently co-occur and partially overlap in MS but their underlying biological substrates are unclear. In this study, the relative role of cytokines and hypothalamic-pituitary-adrenal (HPA) axis activity in depression and fatigue were examined in patients with relapsing-remitting MS (RRMS).

Interleukin-17-producing T helper cells in autoimmunity.

With all the incredible progress in scientific research over the past two decades, the trigger of the majority of autoimmune disorders remains largely elusive. Research on the biology of T helper type 17 (T(H)17) cells over the last decade not only clarified previous observations of immune regulations and disease manifestations, but also provided considerable information on the signaling pathways mediating the effects of this lineage and its seemingly dual role in fighting the invading pathogens on one hand, and in frightening the host by inducing chronic inflammation and autoimmunity on the other hand. In this context, recent reports have implicated T(H)17 cells in mediating host defense as well as a growing list of autoimmune diseases in genetically-susceptible individuals.

Autoantibody detection using indirect immunofluorescence on HEp-2 cells.

The detection of autoantibodies is an important element in the diagnosis and monitoring of disease progression in patients with autoimmune diseases. In laboratory diagnostic tests for connective tissue and autoimmune liver diseases, indirect immunofluorescence on HEp-2 cells plays a central role in a multistage diagnostic process. Despite the high quality of diagnostics, findings at different laboratories can differ considerably due to a lack of standardization, as well as subjective factors.

CXCR3 mediates renal Th1 and Th17 immune response in murine lupus nephritis.

Infiltration of T cells into the kidney is a typical feature of human and experimental lupus nephritis that contributes to renal tissue injury. The chemokine receptor CXCR3 is highly expressed on Th1 cells and is supposed to be crucial for their trafficking into inflamed tissues. In this study, we explored the functional role of CXCR3 using the MRL/MpJ-Fas(lpr) (MRL/lpr) mouse model of systemic lupus erythematosus that closely resembles the human disease.

Challenges of automated screening and differentiation of non-organ specific autoantibodies on HEp-2 cells.

Analysis of autoantibodies (AAB) by indirect immunofluorescence (IIF) remains the hallmark of diagnosing autoimmune diseases despite the introduction of multiplex techniques. Non-organ specific AAB are screened in routine diagnostics by IIF on HEp-2 cells. However, IIF results vary due to objective (e.

Standardization of autoimmune diagnostics in Germany: activities of the German group in the European Autoimmune Standardization Initiative.

The German Regional Group of EASI was established during the annual Meeting of the German Society of Immunology in Kiel in September 2005. Since this initial informative meeting, an active core group of about a dozen rheumatologists, immunologists, and laboratory specialists has been generating starter projects. In general, these projects do focus on clinically associated diagnostic questions, and do integrate a variety of specialists with profound knowledge in several related subjects.

Cloning and characterization of an adenoviral vector for highly efficient and doxycycline-suppressible expression of bioactive human single-chain interleukin 12 in colon cancer.

Background: Interleukin-12 (IL-12) is well characterized to induce cellular antitumoral immunity by activation of NK-cells and T-lymphocytes. However, systemic administration of recombinant human IL-12 resulted in severe toxicity without perceptible therapeutic benefit. Even though intratumoral expression of IL-12 leads to tumor regression and long-term survival in a variety of animal models, clinical trials have not yet shown a significant therapeutic benefit.

FK778 in experimental xenotransplantation: a detailed analysis of drug efficacy.

Background: This study examines the efficacy of FK778 regimens for prevention of different phases of xenograft rejection.

Methods: Antibody and complement tissue depositions were measured by immunofluorescence in a discordant ex vivo rat-to-human heart perfusion model of hyperacute rejection with immunosuppressant-enriched human blood. The concordant hamster-to-rat aortic xenotransplantation model was used to assess host cellular (lymphocyte activation, mixed lymphocyte reaction [MLR]) and humoral responsiveness (xenoantibody production) as well as histologic xenograft rejection.